Since the sixties of the last century it has been proposed to use the specific binding power of the immune system (T-cells and antibodies) to selectively kill tumor cells but leave alone the normal cells in a patient's body. Many tumor antigens that could be targeted by in particular antibodies, like carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and so on have been suggested since those days, but for essentially all of these antigens expression is associated with normal tissue as well. Thus, so far this has been an elusive goal.
In an earlier application WO2007/073147 (Apoptosis-inducing protein complexes and therapeutic use thereof incorporated herein by reference) disclosed is a polypeptide complex comprising at least six polypeptides in which polypeptides were assembled to form the complex via post-translational covalent or non-covalent non-peptide bond based linker chemistry. Although such a complex achieves the goal of (specifically) killing, e.g., tumor cells by inducing apoptosis in these tumor cells (although not wishing to be bound by theory, at present it is believed that this is the result of cross-linking), it is quite difficult to produce, since it requires post-translational assembly of polypeptides in functional complexes after expression thereof. In addition the stability of such a complex in vivo may be an issue of concern.